Rostoker G, Rymer J C, Bagnard G, Petit-Phar M, Griuncelli M, Pilatte Y
Service de Néphrologie et Laboratoire d'Investigation Clinique, Hôpital Claude Galien, Quincy sous Sénart; Unité Inserm U 139. France.
Clin Exp Immunol. 1998 Dec;114(3):468-76. doi: 10.1046/j.1365-2249.1998.00745.x.
Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index alpha-55,75 used to assess biologically available TNF-alpha (ratio of total TNF-alpha divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-alpha, TNF index alpha-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-alpha and TNF index alpha-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch-Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.
近期实验数据表明循环促炎细胞因子对IgA肾病的组织学损伤有加重作用，据此，我们研究了多价免疫球蛋白治疗患者血清促炎细胞因子及其可溶性受体和拮抗剂的变化（15例严重肾病患者，有预后不良指标：大量蛋白尿、高血压、肾功能改变及Lee组织学分级III或IV级；14例中度IgA肾病患者，持续性白蛋白尿>300mg/天且<2000mg/天，Lee组织学分级II级，肾小球滤过率>70ml/分钟），并与健康对照者（n = 20）和非IgA肾病患者（n = 50）进行比较。在免疫球蛋白治疗9个月前后，通过特异性免疫测定法对这些指标进行了检测。与对照组相比，IgA肾病患者治疗前血清总肿瘤坏死因子（TNF）和IL-6水平升高，免疫球蛋白治疗后恢复正常。免疫球蛋白治疗后，I型（sR55）和II型（sR75）可溶性TNF受体水平升高。用于评估生物可利用TNF-α的TNF指数α-55,75（总TNF-α除以可溶性TNF受体sR55和sR75水平的比值）在治疗前升高，免疫球蛋白给药9个月后低于健康对照值。严重IgA肾病患者免疫球蛋白给药前血清IL-1受体拮抗剂水平较低，治疗后恢复正常。血清干扰素-γ未发生改变。组织学活动指数与血清总TNF-α、TNF指数α-55,75和血清IL-6水平相关，而蛋白尿与血清总TNF-α和TNF指数α-55,75相关，但与血清IL-6无关。这些数据表明，在IgA肾病和过敏性紫癜性肾炎中，促炎细胞因子的过度产生未被其天然拮抗剂平衡。这一过程可能在疾病进展中起作用，并且是免疫球蛋白治疗的靶点之一。
